Rol de motores moleculares y tráfico vesicular en el establecimiento de la polaridad neuronal. Molecular motors and vesicle trafficking role in neuronal polarity establishment.

En los últimos años se ha establecido que un gran número de enfermedades neurodegenerativas están asociadas a defectos en el transporte vesicular, particularmente aquel mediado por motores moleculares y proteínas quinasas, estando directamente relacionado al establecimiento y mantenimiento de la polaridad neuronal.El estudio de los mecanismos moleculares que regulan la formación y diferenciación de dendritas, especialmente a nivel del tráfico de organelas túbulo-vesiculares, nos permitirá entender el papel de los motores moleculares retrógrados y de las proteínas quinasas en el establecimiento de la polaridad neuronal, evento crucial para el mantenimiento y función del sistema nervioso.Para ello contamos con las herramientas necesarias para el estudio del transporte de proteínas a nivel molecular y celular, como cDNAs para expresar varias proteínas de estudio, siRNAs para bloquear la expresión de proteínas específicas, dominantes negativos y constitutivamente activos de algunos de los componentes a analizar, así como anticuerpos que nos permitan monitorear su localización celular, para lo cual contamos con equipos de microscopía de última generación.Es de esperar que se obtengan resultados que confirmen el papel específico de motores retrógrados, como dineína, y quinasas de las familias C y D, en el transporte de proteínas de membrana al compartimiento somato-dendrítico, demostrando su importancia en el establecimiento de la polaridad neuronal. Entender el desarrollo y el mantenimiento de esta polaridad axón-dendrita es de vital importancia, tanto para incrementar el conocimiento del funcionamiento y la biología del sistema nervioso, como para comprender aquellos mecanismos que se desarrollan en ciertas enfermedades neurodegenerativas y neuropsiquiátricas.

Kohlenwasserstoff-Emissionen eines Motors mit Benzin-Direkteinspritzung und wandgeführtem Brennverfahren

Hydrocarbon, HC, emissions, gasoline direct injection, stratified, mixture building, hc-model, simulation, flame-quenching, wall-quenching, liquid film building

Anisotropy effects during unstable step flow growth

Step flow growth, meandering instability, coarsening

Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.

Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.

Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?

BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

Step this way for better health

This leaflet explains how to use a step counter to motivate yourself to do more walking. It includes a step log to encourage walkers to monitor and record their progress.

Sistema per protegir la privadesa dels usuaris dels motors de cerca d'Internet

Actualment seria impensable la existència d'una xarxa d'informació com Internet sense la existència dels motors de cerca. Gràcies a ells, qualsevol usuari tenim al nostre abast la possibilitat d'obtenir informació sobre qualsevol tema només enviant una consulta des dels nostres ordinadors i rebent una resposta en qüestió de segons. Entre els usuaris dels cercadors d'Internet és molt habitual que les consultes facin referència a la empresa on treballem, la ciutat on vivim, els llocs que visitem, o inclús sobre problemes que tenim o malalties que patim amb l'objectiu de trobar opinions, consells o solucions. En resum, els usuaris, a través de les nostres consultes, proporcionem a diari als motors de cerca informació sobre nosaltres mateixos i sobre la nostra identitat que, juntament amb la adreça IP de la màquina des d'on fem les nostres consultes, ens fa perdre l'anonimat dins dels seus sistemes. Sobre aquesta problemàtica és del que tracta el present Projecte de Final de Carrera. En ell s'ha implementat una solució de la proposta especificada per Alexandre Viejo i Jordi Castellà-Roca en la seva publicació "Using social networks to disort users' profiles generated by web search engines", en la qual es documenten una sèrie de protocols de seguretat i d'algorismes de protecció i distribució que garanteixen la privacitat de la identitat dels usuaris dins dels motors de cerca aprofitant per aquest fi la relació existent entre aquests usuaris a través de les xarxes socials.

Bowel cancer screening: the next step (English and 10 translations)

Format: 4 page A5 leaflet Target group: Participants in the Northern Ireland Bowel cancer screening programme who require further investigations Description: This leaflet provides information on further investigations participants may require, including colonoscopy.

Bonding and Bridging Social Capital in Step- and First-Time Families and the Issue of Family Boundaries

Divorce and remarriage usually imply a redefinition of family boundaries, with consequences for the production and availability of social capital. This research shows that bonding and bridging social capitals are differentially made available by families. It first hypothesizes that bridging social capital is more likely to be developed in stepfamilies, and bonding social capital in first-time families. Second, the boundaries of family configurations are expected to vary within stepfamilies and within first-time families creating a diversity of family configurations within both structures. Third, in both cases, social capital is expected to depend on the ways in which their family boundaries are set up by individuals by including or excluding ex-partners, new partner's children, siblings, and other family ties. The study is based on a sample of 300 female respondents who have at least one child of their own between 5 and 13 years, 150 from a stepfamily structure and 150 from a first-time family structure. Social capital is empirically operationalized as perceived emotional support in family networks. The results show that individuals in first-time families more often develop bonding social capital and individuals in stepfamilies bridging social capital. In both cases, however, individuals in family configurations based on close blood and conjugal ties more frequently develop bonding social capital, whereas individuals in family configurations based on in-law, stepfamily or friendship ties are more likely to develop bridging social capital.

A Step in the Right Direction: An Evaluation of the Fáiltiú Information and Advise Service

The Fáiltiú service provides information and advice on rights, entitlements and options to homeless people, or those at risk of homelessness. The objectives of this evaluation were to assess the information needs of users of the service, how effectively they were being met, and how they could be improved. Two focus groups of staff members and service users gave their views on the design and implementation of the research at the outset of the project. A screening questionnaire identified 78 people who used the Fáiltiú service in a specified time period, of whom 40 participated in the evaluation by giving their views on the service. The study reviewed the literature on homelessness, attempted to define the term, and examined the characteristics of homeless people and relevant Irish social policy. The conclusions reached were: users of the Fáiltiú service are marginalized in a number of ways and share characteristics related to poverty and social exclusion, such as poor educational qualifications, high levels of unemployment and experience of prison; their needs are multi-dimensional and include accommodation, financial, social and medical support, and access to employment and training services: the service needs to respond to these needs in a holistic way.This resource was contributed by The National Documentation Centre on Drug Use.

Regional-scale integration of multi-scale hydrological and geophysical data using a two-step Bayesian sequential simulation approach

Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale for the purpose of improving predictions of groundwater flow and solute transport. However, extending corresponding approaches to the regional scale still represents one of the major challenges in the domain of hydrogeophysics. To address this problem, we have developed a regional-scale data integration methodology based on a two-step Bayesian sequential simulation approach. Our objective is to generate high-resolution stochastic realizations of the regional-scale hydraulic conductivity field in the common case where there exist spatially exhaustive but poorly resolved measurements of a related geophysical parameter, as well as highly resolved but spatially sparse collocated measurements of this geophysical parameter and the hydraulic conductivity. To integrate this multi-scale, multi-parameter database, we first link the low- and high-resolution geophysical data via a stochastic downscaling procedure. This is followed by relating the downscaled geophysical data to the high-resolution hydraulic conductivity distribution. After outlining the general methodology of the approach, we demonstrate its application to a realistic synthetic example where we consider as data high-resolution measurements of the hydraulic and electrical conductivities at a small number of borehole locations, as well as spatially exhaustive, low-resolution estimates of the electrical conductivity obtained from surface-based electrical resistivity tomography. The different stochastic realizations of the hydraulic conductivity field obtained using our procedure are validated by comparing their solute transport behaviour with that of the underlying ?true? hydraulic conductivity field. We find that, even in the presence of strong subsurface heterogeneity, our proposed procedure allows for the generation of faithful representations of the regional-scale hydraulic conductivity structure and reliable predictions of solute transport over long, regional-scale distances.